1. Field of the Invention
The present invention relates to methods of non-invasively determining the pulmonary capillary blood flow of a patient. Particularly, the present invention relates to re-breathing techniques for measuring the pulmonary capillary blood flow of a patient. More particularly, the methods of the present invention account for changes in the carbon dioxide content of the venous blood of a patient or in the cardiac output of a patient that may occur during re-breathing.
2. Background of Related Art
Cardiac output, the volume of blood that is pumped by the heart over a set period of time, includes two components, pulmonary capillary blood flow (Q.sub.pcbf) and intrapulmonary shunt (Q.sub.s). Pulmonary capillary blood flow is the volume of blood (typically measured in liters) that participates in the exchange of blood gases over a set period of time (typically one minute). Cardiac output is typically measured during surgery or while a patient is under intensive care, and indicates the cardiovascular condition of the patient and the patient's response to medical intervention. Conventionally, cardiac output has been measured by both invasive and non-invasive techniques.
Indicator dilution, an exemplary invasive, typically intermittent technique for measuring cardiac output, includes introducing a predetermined amount of an indicator into a single point of the bloodstream of a patient and analyzing blood downstream from the point of introduction to obtain a time vs. dilution curve. Thermodilution, in which saline solution at room temperature or a colder temperature, which may also be referred to as "cold" saline, is employed as the indicator, is a widely employed type of indicator dilution. Typically, the cold saline is introduced into the right heart bloodstream of a patient through a thermodilution catheter, which includes a thermistor at an end thereof. The thermistor is employed to measure the temperature of the blood after it has passed through the right heart, or downstream from the point at which the cold saline is introduced. A thermodilution curve is then generated from the data, from which the cardiac output of the patient may be derived. Thermodilution and other indicator dilution techniques are, however, somewhat undesirable due to the potential for harm to the patient that is associated by inserting and maintaining such catheters in place.
Conventional, so-called "non-invasive" techniques for determining the cardiac output of a patient typically include a pulmonary capillary blood flow measurement according to the Fick principle: the rate of uptake of a substance by or release of a substance from blood at the lung is equal to the blood flow past the lung and the content difference of the substance at each side of the lung. The Fick principle may be represented in terms of oxygen (O.sub.2) by the following formula: EQU Q=VO.sub.2 /(CaO.sub.2 -CVO.sub.2),
where Q is the cardiac output of the patient, VO.sub.2 is the volume of oxygen consumed by the patient per unit of time, CaO.sub.2 is the O.sub.2 content of the arterial, or oxygenated, blood of the patient, and CVO.sub.2 is the O.sub.2 content of the venous, or de-oxygenated, blood of the patient. The oxygen Fick principle may be employed in calculating the cardiac output of a patient either intermittently or continuously. The intrapulmonary shunt flow may also be estimated, and subtracted from the cardiac output to determine the pulmonary capillary blood flow of the patient.
An exemplary method of determining the cardiac output of a patient by monitoring VO.sub.2 is disclosed in Davies et al., Continuous Fick cardiac output compared to thermodilution cardiac output, Crit. Care Med. 1986; 14:881-885 ("Davies"). The method of Davies includes continually measuring the O.sub.2 content of samples of gas inspired and expired by a patient, the oxygen saturation (SVO.sub.2) of the patient's venous blood, and oxygen saturation (SaO.sub.2) of the patient's arterial blood. The O.sub.2 measurements are made by a metabolic gas monitor, and VO.sub.2 calculated from these measurements. SaO.sub.2 is measured by pulse oximetry. SVO.sub.2 is directly measured by a pulmonary artery ("PA") catheter. Each of these values is then incorporated into the oxygen Fick equation to determine the cardiac output of the patient. Although the method of Davies may be employed to intermittently or continuously determine the cardiac output of a patient, it is somewhat undesirable from the standpoint that accurate VO.sub.2 measurements are typically difficult to obtain, especially when the patient requires an elevated fraction of inspired oxygen (FiO.sub.2). Moreover, since the method disclosed in Davies requires continual measurement of SVO.sub.2 with a pulmonary artery catheter, it is an invasive technique.
Due in part to the ease with which the carbon dioxide elimination (VCO.sub.2) of a patient may be accurately measured, VCO.sub.2 measurements may be employed in methods of non-invasively determining the pulmonary capillary blood flow of a patient. Since the respiratory quotient (RQ) is the ratio of carbon dioxide elimination to the amount of oxygen inhaled, VCO.sub.2 may be substituted for VO.sub.2 according to the following equation: EQU VO.sub.2 =VCO.sub.2 /RQ.
Alternatively, a modification of the Fick principle, which is based on the exchange of carbon dioxide (CO.sub.2) in the lungs of a patient, has been employed to calculate the pulmonary capillary blood flow of the patient. The carbon dioxide Fick equation, which represents the Fick principle in terms of CO.sub.2 elimination and exchange, follows: EQU Q=VCO.sub.2 /(CVCO.sub.2 -CaCO.sub.2),
where VCO.sub.2 is the carbon dioxide elimination of the patient, CVCO.sub.2 is the content, or concentration, of CO.sub.2 in the venous blood of the patient, and CaCO.sub.2 is the content, or concentration, of CO.sub.2 in the arterial blood of the patient. The difference between CVCO.sub.2 and CaCO.sub.2 is typically referred to as the arterial-venous gradient, or "AV gradient".
The carbon dioxide Fick equation has been employed to non-invasively determine the pulmonary capillary blood flow and cardiac output of a patient on an intermittent basis. The carbon dioxide elimination of the patient may be non-invasively measured as the difference per breath between the volume of carbon dioxide inhaled during inspiration and the volume of carbon dioxide exhaled during expiration, and is typically calculated as the integral of the carbon dioxide signal times the rate of flow over an entire breath. The volume of carbon dioxide inhaled and exhaled may each be corrected for any deadspace.
The partial pressure of end-tidal carbon dioxide (PetCO.sub.2 or etCO.sub.2) is also measured in re-breathing processes. The partial pressure of end tidal carbon dioxide, after correcting for any deadspace, is typically assumed to be approximately equal to the partial pressure of carbon dioxide in the alveoli (PACO.sub.2) of the patient or, if there is no intrapulmonary shunt, the partial pressure of carbon dioxide in the arterial blood of the patient (PaCO.sub.2).
Re-breathing is typically employed either to non-invasively estimate the carbon dioxide content of mixed venous blood (in total re-breathing) or to obviate the need to know the carbon dioxide content of the mixed venous blood (by partial re-breathing). Re-breathing processes typically include the inhalation of a gas mixture which includes carbon dioxide. During re-breathing, the CO.sub.2 elimination of the patient is less than during normal breathing. Re-breathing during which the CO.sub.2 elimination decreases to near zero is typically referred to as total re-breathing. Re-breathing that causes some decrease, but not a total cessation of CO.sub.2 elimination, is typically referred to as partial re-breathing.
Re-breathing is typically conducted with a re-breathing circuit, which causes a patient to inhale a gas mixture that includes carbon dioxide. FIG. 1 schematically illustrates an exemplary re-breathing circuit 50 that includes a tubular airway 52 that communicates air flow to and from the lungs of a patient. Tubular airway 52 may be placed in communication with the trachea of the patient by known intubation processes, or by connection to a breathing mask positioned over the nose and/or mouth of the patient. A flow meter 72, which is typically referred to as a pneumotachometer, and a carbon dioxide sensor 74, which is typically referred to as a capnometer, are disposed between tubular airway 52 and a length of hose 60, and are exposed to any air that flows through re-breathing circuit 50. Both ends of another length of hose, which is referred to as deadspace 70, communicate with hose 60. The two ends of deadspace 70 are separated from one another by a two-way valve 68, which may be positioned to direct the flow of air through deadspace 70. Deadspace 70 may also include an expandable section 62. A Y-piece 58, disposed on hose 60 opposite flow meter 72 and carbon dioxide sensor 74, facilitates the connection of an inspiratory hose 54 and an expiratory hose 56 to re-breathing circuit 50 and the flow communication of the inspiratory hose 54 and expiratory hose 56 with hose 60. During inhalation, gas flows into inspiratory hose 54 from the atmosphere or a ventilator (not shown). During normal breathing, valve 68 is positioned to prevent inhaled and exhaled air from flowing through deadspace 70. During re-breathing, valve 68 is positioned to direct the flow of exhaled and inhaled gases through deadspace 70.
During total re-breathing, substantially all of the gas inhaled by the patient was expired during the previous breath. During total re-breathing, the partial pressure of end-tidal carbon dioxide is typically assumed to be equal to the partial pressure of carbon dioxide in the venous blood (PVCO.sub.2) of the patient, as well as to the partial pressure of carbon dioxide in the arterial blood (PaCO.sub.2) and the partial pressure of carbon dioxide in the alveolar blood (PACO.sub.2) of the patient. Total re-breathing processes are based on the assumption that neither pulmonary capillary blood flow nor the content of carbon dioxide in the venous blood of the patient (CVCO.sub.2) change substantially during the re-breathing process. The partial pressure of carbon dioxide in blood may be converted to the content of carbon dioxide in blood by means of a carbon dioxide dissociation curve. The carbon dioxide form of the Fick equation, in which CVCO.sub.2 and CaCO.sub.2 are variables, may be employed to determine pulmonary capillary blood flow.
In partial re-breathing, the patient inhales a mixture of gases exhaled during the previous breath and "fresh" gases. Thus, the patient does not inhale as much carbon dioxide as would be inhaled during a total re-breathing process. Conventional partial re-breathing processes typically employ a differential form of the carbon dioxide Fick equation to determine the pulmonary capillary blood flow of the patient, which does not require knowledge of the carbon dioxide content of the mixed venous blood. This differential form of the carbon dioxide Fick equation considers measurements of carbon dioxide elimination (VCO.sub.2), CVCO.sub.2, and the content of carbon dioxide in the alveolar blood of the patient (CACO.sub.2) during both normal breathing and the re-breathing process as follows: ##EQU1##
where VCO.sub.2 B and VCO.sub.2 D are the carbon dioxide elimination of the patient before re-breathing and during the re-breathing process, respectively, CVCO.sub.2 B and CVCO.sub.2 D are the contents of CO.sub.2 of the venous blood of the patient before re-breathing and during the re-breathing process, respectively, and CACO.sub.2 B and CACO.sub.2 D are the contents of CO.sub.2 in the alveolar blood (i.e., the blood in the capillaries that surround the alveoli) of the patient before re-breathing and during the re-breathing process, respectively. The alveolar partial pressures of carbon dioxide may then be converted to the carbon dioxide contents of the patient's alveolar blood by means of a carbon dioxide dissociation curve. During conventional re-breathing processes, the pulmonary capillary blood flow and CVCO.sub.2 of a patient are assumed to remain substantially unchanged. The latter assumption causes the CVCO.sub.2 terms of the preceding equation to cancel each other, but is somewhat undesirable because it may introduce error into the cardiac output determination since CVCO.sub.2 may change during re-breathing.
Alternative differential Fick methods of measuring pulmonary capillary blood flow or cardiac output have also been employed. Such differential Fick methods typically include a brief change of PetCO.sub.2 and VCO.sub.2 in response to a change in effective ventilation. This brief change can be accomplished by adjusting the respiratory rate, inspiratory and/or expiratory times, or tidal volume. A brief change in effective ventilation may also be effected by adding CO.sub.2, either directly or by re-breathing. An exemplary differential Fick method that has been employed, which is disclosed in Gedeon, A. et al. in 18 Med. & Biol. Eng. & Comput. 411-418 (1980), employs a period of increased ventilation followed immediately by a period of decreased ventilation.
Cardiac output, which is also assumed to remain constant in many conventional re-breathing techniques, may also change during re-breathing. In fact, changes in cardiac output during re-breathing are known to be more common than changes in CVCO.sub.2. As with the undesirability of the assumption that CVCO.sub.2 remains constant during re-breathing, the assumption that cardiac output is constant may lead to inaccuracies in the cardiac output determination.
Accordingly, an accurate, non-invasive method of determining the pulmonary capillary blood flow or cardiac output of a patient is needed that compensates for changes in the carbon dioxide content of the venous blood of a patient during re-breathing or for changes in the cardiac output of the patient during re-breathing.